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Tryptophan hydroxylase 2

TPH2, tryptophan hydroxylase-2

This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. The human genome contains two related tryptophan hydroxylases, one on chromosome 11p15-p14 and one on chromosome 12q21. This gene is expressed predominantly in the brain stem. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Jul 2008] (from
NCBI)

The aim of this study was to investigate the relationship between genotypic variation in six candidate serotonergic genes (ADCY9, HTR1B, GNB3, HTR2A, TPH2, SLC6A4) and depressive and anxiety symptom severity trajectories as well as remission following escitalopram treatment.

This paper attempts to provide a comprehensive review of available imaging genetics studies, including reports on genetic variants that have most frequently been linked to MDD, such as the monoaminergic genes (serotonin transporter gene, monoamine oxidase A gene, tryptophan hydroxylase-2 gene, serotonin receptor 1A gene and catechol-O-methyl transferase gene), with regard to key structures involved in emotion processing, such as the hippocampus, amygdala, anterior cingulate cortex and orbitofrontal cortex.

The serotonin neurons express a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2, exhibit typical electrophysiological properties and release serotonin in an activity-dependent manner.

The treatment did not modify hippocampal tryptophan hydroxylase 2, a serotonergic indicator, but induced an initial reduction in dopaminergic markers in substantia nigra, which remained stable for at least 3 months.

In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2).

Current evidence suggests that genetic variability of the serotonergic biosynthesis enzyme tryptophan hydroxylase 2 (TPH2) and the serotonin transporter (SLC6A4) genes mediates the efficacy of several addiction treatments, such as ondansetron and disulfiram, and the antidepressants bupropion, nortriptyline and sertraline.

Both short-term stress and acute DEX administration, in parallel with Bcl-xL, caused a significant increase in tph2 mRNA levels and slightly enhanced tryptophan hydroxylase immunoreactivity in the midbrain.

The review provides evidence that: 1) genes encoding key elements of the brain serotonergic system (tryptophan hydroxylase-2, 5-HT1A and 5-HT2A receptors) are implicated in the effect ofBDNF; 2) acute central administration of BDNF produced long-term ameliorative effects on some animal models of genetically defined behavior disorders; 3) BDNF decreased behavioral disorders induced by prenatal stress and ethanol exposure and may play an important role in the treatment of epigenetically defined pathological behavior.